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Something I did was install a mod that allows only people who have made 10 or more posts can post links or have signatures.

I also set up a promotion system to that a new members go into a newbie group and they have very limited rights in posting. Once they have made certain number of posts they are promoted to registered member status.

Most spammers have less than 10 posts when they post spam unless you allow it to go on long term without banning the account used.

I would do this in addition to the other recommendations. Lookup spam in vbulletin mods at vbulletin.org and you should find what you need.

I also recommend not using captcha as spammers are building ocr systems that get by that. Make them answer simple human questions instead, such as what is the middle letter in the word red, but make your questions pop up at random and change them regularly.

1. Take off the website field. That reduces comments by more than half.
2. Math protection works good. use it in conjunction with akismet
3. If you get too many spam comments from the same ip/email use an ip ban plugin to block them

I already have installed akismet but it asks signing up and other process. That is why I avoided it. But about the math plugin, I am getting reports/notifications in my email of even more comments being posted after installing that plugin. Maybe they found a way to bypass those math questions. The other thing amazing is that though I get notification of comments in my email the pending comments number is always 16. May be the comments are being posted without my approval.
But It should have been possible to stop comment at all if you want so in the settings section. I have another WP site and below every post it says "comments are closed"
Though I tried to duplicate what I did there then I couldn't. Now I think I have to try Akismet. I will report back after I did.

Akismet blocks around 800 - 900 spam comments on my blog on a daily basis - I cant imagine what would happen if it wasnt there to help me out. Its the best option to arrest spam mainly because it has the largest database and it is from the developers of Wordpress. If your website is personal then akismet offers a free license but for pros it is made a paid version for a small amount but a great service.

Like most users have suggested already, you should go with Akismet, it is very quick and easy to get and set up your key. There also many plugins that can be used to complement the functionality of akismet. One such is the Math Comment Spam Protection which has also been mentioned earlier, these are both free and will greatly assist you.
If however your site is large multi user one where you are getting new users daily and then they abuse this privilege to post spam comments (mostly bot registrations),
then I would recommend SABRE - a very powerful anti-bot registration plugin.

Thanks guys. I think Akismet saved me. I have only 1 notification of coment in my email after I installed that plugin. The reason I did not activate was because it asks for signing up and inputing API key in a form in the plugin. Man am I Lazzzy. Thx guys.

1. Akismet: comes with wordpress and works great.
2. Growmap Anti Spambot Plugin: It is also great. It adds a check box just before the submit button so, only thing that genuine commenter have to do is a simple click. Check how it works on my blog http://www.crazyblogger.info

I suggest that you don't use captcha because I hate it, I guess you hate it too and almost all people on the web hate it as well.

Another thing you can do on wordpress is to disable comment on post older than certain days. You can find this setting on yoursite.com/wp-admin/options-discussion.php I have set it to 365 days but you might make it less it you are getting a lot of spam comments.